This invention relates to the field of nutritional supplements, including supplements which elevate release of human growth hormone.
1. Background of the Invention
Until recently human growth hormone (hereinafter alternatively referred to as hGH) was available only in expensive injectable forms and benefits from the restoration of hGH levels available only to those with the ability to pay. Most recently natural substances which can trigger the release of human growth hormone from an individual""s own anterior pituitary gland have become available. These are generically referred to as secretagogues. Secretagogues have the ability to restore hGII levels, potentially to the levels found in youth. See for reference the book entitled xe2x80x9cGrow Young With hGIIxe2x80x9d by Dr. Ronald Klatz, President of the American Academy of Anti-Aging, published in 1997 by Harper Collins.
In 1981 a study was published by Drs. Isidori, A., Lo Monico and Cappa (Isidori, A., et al. Current Medical Research and Opinion 7 # 7 (1981):475-481) which demonstrated that a specific combination of amino acids, when ingested orally, would cause an increase in growth hormone levels in humans. If offered a more practical and physiological approach to the previously known fact that intravenous administration of amino acids strongly stimulates the secretion of human growth hormone by the anterior pituitary gland.
Franco Salomon et al [The New England Journal of Medicine Vol. 321 (26) p.1797-1803) 1989] carried out a 6 month randomized, double blind, placebo controlled trial of recombinant human growth hormone on 24 patients suffering from growth hormone deficiency. They noticed an increase in Insulin-like Growth Factor 1 (xe2x80x9cIGF-1xe2x80x9d), lean body mass and reduction in fat. Metabolic rate was increased and plasma cholesterol lowered.
JO. L. Jorgensen et al (Lancet-Jun. 3rd, 1989 p. 1221-1225) carried out a 4 month double blind, placebo controlled, crossover study of growth hormone in 22 deficient adults. Muscle thickness increased, fat was reduced. Renal plasma flow and glomerular filtration rates were raised from subnormal levels to levels comparable for their age. IGF-1 levels were also normalized.
In 1990 Dr. Daniel Rudman published a research paper (Rudman, D., et al. xe2x80x9cEffects of Human growth Hormone in men over 60 years Oldxe2x80x9d, New England Journal of Medicine, 323 (1990): 1-6) which showed that twelve healthy men aged between 61 and 81, following six months of human growth hormone therapy, had age reversal effects on lean body mass and adipose tissue mass equivalent in magnitude to changes attributable to ten to twenty years of aging. In addition, Dr. Rudman et al noted that alterations in body composition, caused by growth hormone deficiency as we age, can be reversed by replacement doses of hormone in other experiments in rodents, children and adults 20 to 50 years old. Dr. Rudman also noted that xe2x80x9cthese findings suggest that the atrophy of the lean body mass and its (the body""s) component organs and the enlargement of the mass of adipose tissue that are characteristic of the elderly results at least in part from diminished secretion of growth hormone. If so, the age-related changes in body composition should be correctable in part by the administration of human growth hormone, now readily available as a bio-synthetic productxe2x80x9d.
The primary purpose of hGH is that of stimulating growth, cell repair and regeneration. Once the growth period is over, its primary function becomes that of cell regeneration and repair, helping to regenerate skin, bones, heart, lungs, liver and kidneys to their former youthful cell levels. Elevating hGH levels appears to benefit the immune system. It has also been reported the risk factors for heart attack and stroke may be potentially diminished. Some patients with emphysema have reported that they are less short of breath. Dr. Rudman""s study also demonstrated that bone density in the lumbar spine can improve. It has also been shown that wrinkled skin diminishes. Others have reported improvement in presbyopia (the difficulty in focussing due to hardening of the lenses as we age) with some reporting restoration of hair colour and growth. hGH appears to selectively reduce the fat around the abdomen, hips, waist and thighs while at the same time increasing muscle mass. In Dr. Rudman""s study, after six months of usage, without exercise, the subjects had an average 8% increase in lean muscle mass and a 14.4% loss of fat.
Dr. Cass Terry and Dr. E. Chein reported on the effects of elevating hGH levels by injection. They showed high frequency-low dose injections of hGII elevated IGF-1 levels. Analyzing the clinical effects of elevating hGH in 202 patients (age 39-74) they showed 75% of the individuals described an increase and improvement in sexual potency as well as frequency of sexual relations, while 62% described improvement in duration of penile erection. Energy levels were improved in 84% of individuals and muscle strength improved in 88%. A 71% increase in healing capacity was noted.
It appears that hGH not only has the ability to restore sexual potency and sexuality in older men, but acts as a mood elevator, restoring a youthful sense of wellness as well as improving sleep. With its potential for affecting cell regeneration and repair, healing of injuries should improve.
hGH, alternatively referred to herein by its medical name Somatotropin, is produced in the anterior pituitary gland situated just below the hypothalamus which is itself situated just below the cerebral cortex of the brain. hGH is one of several hormones secreted by the anterior pituitary gland and, as noted above, influences the growth, regeneration and repair of cells, bones, muscles and organs throughout the body throughout life. Production peaks at adolescence when accelerated growth is occurring and if growing children are deficient in human growth hormone, they remain as pituitary dwarfs. If they have too much they exhibit gigantism (acromegaly).
As is the case with many of our other hormones or their pre-cursors, such as testosterone, oestrogen, progesterone, DHEA and melatonin, hGH levels decline with age. Therapeutically, many of these hormones can be replaced to offset some of the effects of aging such as menopausal symptoms in women or erectile dysfunction in men.
The human body, like every other living entity, works on a daily, or circadian as well as monthly and annual rhythms. Daily growth hormone secretion diminishes with age with roughly half the levels at age forty that we had when we were twenty, and about one-third of those youthful levels at age sixty. In some sixty-year olds the levels are as low as 25% of the hGH levels in a twenty-year old. Symptoms of aging include loss of muscle, increase of fat, decreased physical mobility, decreased energy levels and as a result, diminished socialization, diminished healing ability and an increased risk of cardiovascular disease and decreased life expectancy.
Low hGH levels are associated with the aging process and early onset of disease. For example, Rosen and Bengtsson noted an increased death rate from cardiovascular disease in hGH deficient patients (Rosen, T., Bengtsson, B. A., Lancet 336 (1990): 285-2880). Furthermore, the mechanism of hGH release has been elucidated and is considered to be under the control of Growth Hormone Releasing Hormone (GHRH) and Somatostatin. Somatostatin prevents further release of hGH from the pituitary gland. It has been postulated that one of the key factors in aging is an imbalance in the levels of GHRH and Somatostatin in the combined GHRH/Somatostatin secretion, with an increased action or effectiveness of Somatostatin over GHRH. This leads to an effective reduction in release of the stored hGH from the anterior pituitary gland. Isidori et al have shown the selected amino acids arginine and lysine increase the release of the body""s own stored, natural hGH, when taken orally. Matteini showed even low doses of arginine in the region of 200 mg can elevate hGH release. (Matteini, M., et al. Bollettino-Societa Italiana Biologia Sperimentale. 56(21):2254-60, Nov. 15, 1980). It has been suggested one of the mechanisms of action is the inhibitory effect of arginine, and possibly other amino acids, on the secretion and action of Somastostatin (Alba-Roth, J., Muller, O. A., Schopohl, J. et al. Journal of Clinical Endocrinology and Metabolism 67, #6 (1998): 1186-1189).
hGH, once released by the pituitary gland, travels in the circulation and is taken up principally by the liver where it stimulates the production of IGF-1. IGF-1 is then released into the circulation where it attaches to cells in the body and like insulin, triggers the cell to produce certain responses which, with IGF-1, are those of growth, regeneration and repair. Levels of IGF-1 are monitored by the hypothalamus situated just above the pituitary gland. When maximal hGH levels are attained for any individual, these levels trigger the release of Somatostatin. This feedback loop prevents excessive levels of hGH in the body. This feedback loop is extremely efficient at monitoring and maintaining the hGH (and therefore IGF-1) at the optimal level for the individual.
In the prior art, the use of amino acids has essentially been limited to applications where the amino acids have been used as feeding preparations. The amino acids are the final form in which protein is digested from the gastrointestinal tract in mammals. They are essentially pre-digested protein. Given in physiological blends, i.e. those blends that are found occurring naturally in natural proteins such as meat, milk and plants, they can provide the body with the protein nutrients required without the need to pass through the gastrointestinal tract for digestion, i.e. break down to amino acids.
It is thus one object of the present invention to provide a nutritional supplement for elevating hGH release, in particular an amino acid stack, for a synergistic, well tolerated supplemental having the result of increasing or elevating hGH release in those individuals where hGH release rates have slowed as a function of increasing age.
2. Summary of the Invention
The present invention is a nutritional supplement. It is an amino acid stack secretagogue, which, taken orally, stimulates the pituitary gland to produce hGII/Somatotropin. One object of the present invention is to elevate hGH/Somatotropin release. This has the further result of increasing IGF-1 levels. Further objects of the present invention may also result, namely, inhibiting insulin depression; inhibiting hyperglycaemia and increasing insulin effectiveness; enhancing fat conversion, assisting in lowering cholesterol, and normalizing lipid balance.
In summary, the nutritional supplement for restoring growth hormone levels of the present invention comprises in combination, or, alternatively, consists essentially of in combination the following free amino acids (alternatively in the xe2x80x9cLxe2x80x9d form such as L-Glutamine): lysine, ornithine, glutamine, glycine, leucine, iso-leucine, and valine; and may also include arginine.
In one aspect, the present invention is a nutritional supplement for ingestion by humans for restoring growth hormone levels including or alternatively consisting essentially of:
(a) branched chain amino acids chosen from the group leucine, isoleucine, and valine; and
(b) free form amino acids chosen from the group lysine, glutamine, ornithine, arginine, and glycine.
In a further aspect of the present invention, the nutritional supplement for ingestion by humans for restoring growth hormone levels includes or alternatively may consist essentially of all of the amino acids leucine, isoleucine, valine, lysine, glutamine, ornithine and glycine, and may also include arginine.
In a daily dosage the nutritional supplement may include or alternatively consist essentially of:
(a) 1200 mg of L-Lysine;
(b) 1200 mg of L-Arginine;
(c) 798 mg of L-Ornithine;
(d) 498 mg of Glycine;
(e) 240 mg of L-Glutamine;
(f) 420 mg of Leucine;
(g) 420 mg of Iso-Leucine; and
(h) 420 mg of Valine.
In alternative formulations, a daily dosage of the nutritional supplement will include, or consist essentially of:
(a) Lysine in the mass range 500 mg and 1500 mg;
(b) Arginine in the mass range 500 mg and 1500 mg;
(c) Ornithine in the mass range 500 mg and 1500 mg;
(d) Glutamine in the mass range 500 mg and 1000 mg;
(e) Glycine in the mass range 400 mg and 1000 mg;
(f) Leucine in the mass range 400 mg and 1000 mg;
(g) Iso-leucine in the mass range 400 mg and 1000 mg; and
(h) Valine in the mass range 400 mg and 1000 mg.